Alpha diversity analysis of hepatic transcriptome reveals distinct pathways in alcohol-associated hepatitis

Sudrishti Chaudhary; Jia-Jun Liu; Silvia Liu; Marissa Di; Juliane I. Beier; Ramon Bataller; Josepmaria Argemi; Panayiotis V. Benos; Gavin E. Arteel

doi:10.1172/jci.insight.200727

Alpha diversity analysis of hepatic transcriptome reveals distinct pathways in alcohol-associated hepatitis

Sudrishti Chaudhary,¹ Jia-Jun Liu,² Silvia Liu,² Marissa Di,³ Juliane I. Beier,¹ Ramon Bataller,⁴ Josepmaria Argemi,⁵ Panayiotis V. Benos,⁶ and Gavin E. Arteel¹

Published January 8, 2026 - More info

View PDF

Abstract

Next generation sequencing can identify previously uncharacterized gene expression patterns in disease. Beyond differentially expressed genes analysis, we investigated the ability of within-population diversity (α-diversity) of the transcriptome to reveal additional biological information in alcohol-associated liver disease (ALD), comparing Differential Shannon diversity (DSD) to transcriptome heterogeneity changes. RNA sequencing data from normal livers and patients with early ALD and severe AH were analyzed. α-diversity indices and Percent Shannon Diversity of a gene, which refers to this gene's contribution to total Shannon entropy, were calculated. Ingenuity pathway analysis identified canonical pathways determined by differentially expressed genes (DEG) and DSD approaches. ALD significantly decreased hepatic transcriptome α-diversity correlating with increased relative contribution of select genes. These changes were driven by lower abundance gene expression loss. DEG and DSD analyses showed overlapping genes and canonical pathways, but DSD also identified additional genes and pathways not highlighted by DEG, including fatty acid oxidation, extracellular matrix degradation, and cholesterol metabolism pathways that may represent additional therapeutic targets. Importantly, DSD more effectively identified differences between ASH and AH. Overall, α-diversity analysis revealed that ALD progressively reduces transcriptome heterogeneity, and that DSD provides complementary insights into disease mechanisms missed by standard approaches.

Alpha diversity analysis of hepatic transcriptome reveals distinct pathways in alcohol-associated hepatitis

Sudrishti Chaudhary,¹ Jia-Jun Liu,² Silvia Liu,² Marissa Di,³ Juliane I. Beier,¹ Ramon Bataller,⁴ Josepmaria Argemi,⁵ Panayiotis V. Benos,⁶ and Gavin E. Arteel¹

Article tools

Metrics

Go to

Alpha diversity analysis of hepatic transcriptome reveals distinct pathways in alcohol-associated hepatitis

Sudrishti Chaudhary,1 Jia-Jun Liu,2 Silvia Liu,2 Marissa Di,3 Juliane I. Beier,1 Ramon Bataller,4 Josepmaria Argemi,5 Panayiotis V. Benos,6 and Gavin E. Arteel1

Article tools

Metrics

Go to

Sign up for email alerts

Sudrishti Chaudhary,¹ Jia-Jun Liu,² Silvia Liu,² Marissa Di,³ Juliane I. Beier,¹ Ramon Bataller,⁴ Josepmaria Argemi,⁵ Panayiotis V. Benos,⁶ and Gavin E. Arteel¹